Breakthrough Hebrew University Study Identifies Nitric Oxide as Primary Driver in Aggressive Neuroblastoma Growth

New research finds that inhibiting nitric oxide synthase collapses the mTOR pathway in neuroblastoma, offering a potential new strategy for pediatric oncology.

By: AXL Media

Published: Apr 7, 2026, 9:00 AM EDT

Source: Information for this report was sourced from Genomic Press

A Mechanistic Breakthrough for Pediatric Malignancies

A research team led by Professor Haitham Amal at the Hebrew University of Jerusalem has identified a critical molecular "mercenary" responsible for the progression of high-risk neuroblastoma. This aggressive cancer, which originates in the developing fetus, has maintained a stagnant 40% five-year survival rate for decades. The study provides a precise mechanistic explanation for how the signaling molecule nitric oxide (NO) transitions from a quiet biological messenger into a driver of malignancy. By targeting the enzyme neuronal nitric oxide synthase (nNOS), the researchers successfully disrupted the chemical modifications that allow these tumors to grow with such lethal velocity.

The Collapse of the nNOS–mTOR Signaling Axis

The study’s central finding revolves around the systematic collapse of the mTOR signaling pathway when nitric oxide is removed. By using both pharmacological inhibitors and genetic silencing tools, the team observed a 35% to 50% reduction in enzyme activity. This intervention triggered a domino effect: AKT phosphorylation decreased and, most notably, TSC2—the cell’s internal "braking system"—was reengaged. Professor Amal noted that removing the nitric oxide signal allowed the cell to decelerate naturally, effectively releasing the biological accelerator that the cancer had wired to the floor.

Molecular Transformation and the Mirror Experiment

Beyond merely slowing growth, the inhibition of nNOS appeared to strip the cells of their malignant identity. Levels of synaptophysin, a key neuroendocrine tumor marker, fell significantly, suggesting the cells were becoming less recognizably cancerous at a molecular level. To verify these findings, the researchers conducted a "mirror experiment," flooding healthy cells with nitric oxide. The results were perfectly symmetrical; the needle swung in the opposite direction, amplifying the AKT and mTOR pathways and confirming that nitric oxide is a central driver rather than a secondary byproduct of tumor progression.